WHEN A PATIENT'S GENES EXPRESS THEMSELVES, THEY MIGHT: Suggest that a certain treatment is almost sure to work // Signal that heart transplant rejection is imminent // Advise against chemotherapy // Issue other messages we don’t yet understand.

Medicine Gets Personal

Understanding the patient’s genetic makeup is leading to better, more precisely targeted treatments.

Genes first cursed, then blessed Michael Santo. When he arrived at the Massachusetts General Hospital in Boston, in 2002, after falling unconscious at home, he had no doubt his diagnosis would be the same one that had doomed his father. “I know why I’m here,” Santo, now 59, interrupted Tracy T. Batchelor, director of neuro-medical oncology, before Batchelor broke the news of Santo’s brain tumor.

Santo’s father was dead two weeks after his tumor was discovered in 1988. But when Batchelor read the biopsy report on Michael Santo’s tumor, he was elated to find that the tumor’s cells were missing chromosomes 1p and 19q. That meant Santo would almost certainly respond to chemotherapy and could expect to live another decade or more—unlike the 30% of patients with the same tumor but with those two chromosomes intact: They usually succumb within two to three years.

That Batchelor could use the genetic profile of a patient’s tumor to select the right treatment (if the chromosomes weren’t missing, Santo would have been treated with radiation) fulfills one promise of personalized medicine. In an ideal world, this genetics-based revolution would provide fully individualized diagnosis and treatment, enabling doctors to predict what diseases you’ll get and when you’ll get them, as well as to know how to treat them. Someday, far down the road, it might even be possible to pluck out faulty genes and replace them with normal DNA, restoring you to robust health.

In fact, we’re still far from that world. No one can say how long it will take to find the links between variations on some 20,000 human genes and approximately 1,500 diseases. And while genetic and genomic tests are being rushed to market, some predict the onset of diseases for which there’s no effective treatment. Yet, already, remarkable progress has been made, with almost weekly announcements heralding breakthroughs in everything from basic science to immediate applications.

The vision and reality of personalized medicine are separated by 3 billion genetic “letters,” chemical base pairs of DNA that contain instructions for everything a human cell does. The 13-year-long Human Genome Project, completed in 2003, made a monumental contribution, determining the order, in each base pair, of the four chemical bases that make up human DNA. The resulting map provides invaluable information about what makes a human human—rather than a chimpanzee, fruit fly or yeast—and should yield insights into disease patterns and prognoses. Yet, sequencing the genome was only a first step. Rudolph Tanzi, director of the genetics and aging unit at the Massachusetts General Hospital, describes it as providing a phone book of all the genetic suspects that may be implicated in human disease.

“Suppose you’re a detective looking for a serial killer,” Tanzi says. “You now have the book of names of everyone and where they live, but you still have to do old-fashioned detective work—in our case, testing gene variants, looking at inheritance in families—to zero in on the killer and find the smoking gun, the variants on the genes that cause the problems.”

Detecting those smoking guns has been aided by the International HapMap Project, finished last year, that clusters genetic variants into “city blocks,” to continue Tanzi’s analogy. “Now you know which neighborhoods to look in, and you can implicate multiple suspects”—that is, variations on two or three genes that may also be inherited with the disease-causing gene defect you’re after, says Tanzi.

The shift from broad-based methods of diagnosis and treatment to precise, individualized approaches could be slowed by several hurdles, most related to losing the economies of scale that come with treating large populations. Yet solutions are emerging.